This in-vitro study assessed bond strength and micromorphological features of dentin substrates treated with different etching modes using universal adhesive system. A total of 28 freshly extracted human molars with coronal dentin caries were used for this study. A total of 80 composite microcylinders with prepared dentin surface containing both sound dentin and carious affected dentin were divided into two main groups (40 each) according to the bonding mode used: Self-etch mode in one step single dose, and total-etch mode in two steps. Each group was then subdivided into two subgroups (20 specimens each) according to the type of dentin substrate used: Sound dentin and caries affected dentin. For the Scanning Electron Microscope (SEM) examinations, the teeth were divided into two main groups (8 each) according to the bonding mode used: Self-etch mode in one step single dose, and total-etch mode in two steps. Each group was then subdivided into two subgroups (4 specimens each) according to the type of dentin substrate used: sound dentin and caries affected dentin. The interfacial zone was examined using SEM at magnification 5000 X. Data was then recorded, tabulated and statistically analyzed. For sound dentin using total-etch mode (24.02 ± 1.03 MPa) showed statistically significantly lower µSBS than that using self-etch mode (28.04 ± 1.30 MPa) at p<0.05. For caries affected dentin using total-etch mode (18.46 ± 0.86 MPa) showed statistically significantly higher mean µSBS than that using self-etch mode (16.48 ± 0.84 MPa) at p<0.05. Independent of the etch mode used for bonding, sound dentin showed statistically significantly higher mean µSBS than that of caries affected dentin at p<0.05. These results were confirmed by the examination of the SEM images which revealed increase in number and length of resin tags for the groups showing high µSBS. In conclusion, using self-etch universal adhesives on sound dentin is considered to be material dependent. And using total-etch mode of universal adhesive on caries affected dentin can enhance bond strength. Moreover, the type of substrate and etching strategies may affect the bonding performance and durability of restorations in dentistry.